PB1897: GILTERITINIB IN TURKEY: EARLY ACCESS PROGRAM RESULTS
Authors: Mehmet Hilmi Dogu, Ali Irfan Emre Tekgunduz, Burak Deveci, Gulten Korkmaz, Melda Comert, Ömür Gökmen Sevindik, Osman Yokus, Istemi Serin
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: The prognosis is relatively poor in relapsed or refractory (R/R) acute myeloid leukemia (AML) that does not respond to standard chemotherapy after induction therapy. FMS-like tyrosine kinase 3 (FLT3) is expressed in hematopoietic stem cells as a cytokine receptor tyrosine kinase and plays a role in proliferation and differentiation. Gilteritinib (XOSPATA ®, Astellas) is a type I oral FLT3 inhibitor, a tyrosine kinase AXL inhibitor involved in both c-Kit and FLT3 resistance, as well as FLT3-ITD and TKD mutations. Aims: The purpose of this research was to investigate the real-life efficacy and safety of Gilteritinib (XOSPATA ®, Astellas) in FLT3 positive relapsed or refractory acute myeloid leukemias (AML) patients who were treated as a part of early access program which was held in Turkey starting in April 2020 (NCT03409081). Methods: The research included 17 R/R AML cases who had received gilteritinib from a total of 7 centers, allowing the use of their data across Turkey between April 2020 and October 2021. The genetic classification was based on the 2022 ELN risk classification by genetics at initial diagnosis. Patients were required to have either FLT3-ITD or TKD (D835/I836) mutations, and all of the patients were ITD mutants. Responses to gilteritinib were assessed on day 1 of cycle 2. The ORR was defined as complete remission (CR), CR with incomplete platelet counts (CRp), CR with incomplete hematologic recovery (CRi), and partial remission (PR). The preferred dose of gilteritinib was the same in all patients with a daily dose of 120 mg. Results: The mean age of patients at diagnosis was 49.8±13.8 years, whereas the median age was 55 years (range: 27-73). The number of patients who received allogeneic transplantation before gilteritinib use was 2 (11.8%), the number of patients who received allogeneic transplantation after gilteritinib use was 7 (41.2%), and the number of patients who received maintenance therapy after transplantation was 2 (11.8%). The most common adverse events were anemia and hypokalemia (7 patients, 41.2%). Grade 4 thrombocytopenia was observed in only one patient (5.9%) which led to permanent discontinuation of treatment, treatment had to be discontinued, and no other patient experienced any dose reduction or curtailment. The overall response rate (ORR) was 100% (nCR =11, 64.7%; nCRp =3, 17.6%; nCRi = 1, 5.9%; nPR =2, 11.8%). The median duration of use of gilteritinib was 8.5 (range: 1-21) months. The median PFS was 300.5 (range: 15-813) days, and the OS was 355.5 (range: 21-905) days with gilteritinib. The risk of death in patients with febrile neutropenia was 7.36 (95% CI: 1.26-43.05) times higher than that in patients without febrile neutropenia (p<0.05). Patients with peripheral edema had a 10.47 (95% CI: 1.64-66.82) times higher risk of death than those without peripheral edema (p<0.05). Summary/Conclusion: This research showed that patients with febrile neutropenia and peripheral edema were at a high risk of death when compared to patients without febrile neutropenia and peripheral edema. Side effect-survival analyses: A. Febrile neutropenia - progression-free survival (PFS), B. Febrile neutropenia - overall survival (OS), C. Peripheral edema - PFS, D. Peripheral edema - OSKeywords: FLT3, Relapsed acute myeloid leukemia, flt3 inhibitor, Flt3-ITD